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Biomedical subjects

D Franco

Publications and source records attributed to D Franco.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of tumour recurrence after resection of hepatocellular carcinoma. Analysis of 97 consecutive patients.

OBJECTIVE: To evaluate the long-term results of aggressive treatment of HCC recurrence. METHODS: Two hundred and nine consecutive patients underwent hepatic resection for HCC in our hospital. Tumour recurrence was diagnosed in 97 (51%) of the 190 patients with curative resection. Sixteen underwent hepatic resection: two right hepatectomies, one three-segmentectomy, one left hepatectomy, five two-segmentectomies, six segmental resections and one subsegmentectomy. Two patients with metastasis in the spine were submitted to a vertebral body resection. Twenty-five patients were treated with percutaneous ethanol injection or intra-arterial chemoembolization. Fifty-four patients with a poor performance status and liver function or multiple extra hepatic recurrences did not receive any treatment. RESULTS: There were no operative deaths. The postoperative mortality rate was 5.5% (one patient). The cumulative overall survival after the second resection was respectively 89%, 46% and 31% at 1, 3 and 5 years. There was a significant difference in survival between patients treated with repeat resection and those submitted to a non-surgical or conservative treatment (p<0.0001). There were no differences in operative deaths, postoperative mortality and morbidity between the first and second hepatic resection. CONCLUSIONS: Aggressive management with combined resection or loco regional therapy for intrahepatic recurrence and resection of isolated extra-hepatic recurrence may offer long-term survival in selected patients. Second liver resection for recurrence of HCC can be safely performed.

Adolescent↗
PubMed2005

Alternative indicators for monitoring the quality of a continuous intervention program on antibiotic prescribing during changing healthcare conditions.

We recently published on the impact of a four-phase hospital-wide intervention program designed to optimize the quality of antibiotic use, where a multidisciplinary team (MDT) could modify prescription at the last phase. Because health care quality was changing during the last 5 years (late 1999 to early 2004), we developed certain indicators to monitor the quality of our intervention over time. Different periods were defined as baseline (pre-intervention), initial intervention-active control, pre-crisis control, crisis control, post-crisis control and end of crisis control. Major indicators were rates of prescription modification by the MDT; prescription for an uncertain infection and a novel index formula (RIcarb) to estimate the rationale for carbapenem use. We assessed 2115 antimicrobial prescriptions. Modification of prescription rate was 30% at the beginning and decreased thereafter up to stable levels. Rate of prescriptions ordered for cases of both uncertain infection and unknown source of infection decreased significantly after intervention (i.e. from baseline to active control). In contrast, a doubling of culture-directed prescriptions was observed between these periods. RIcarb values lower and higher than 60% (modal, cut-off) were assumed as carbapenem overuse and underuse, respectively. Overuse was observed at the pre-intervention, while pronounced underuse was shown during the crisis (RIcarb, 45% and 87%, respectively). The present study demonstrates that certain indicators, other than the widely adopted impact outcomes, are a suitable tool for monitoring the quality of a continuous, long-term, active intervention on antimicrobial prescribing practice, especially when applied in a changing healthcare setting.

Anti-Bacterial Agents↗
PubMed2002

Low-cost laparoscopic cholecystectomy.

BACKGROUND: Hospital managers are continually trying to decrease the cost of patient care. The aim of this prospective study was to propose changes that would decrease the operating room costs of laparoscopic cholecystectomy without affecting clinical results. METHODS: The study included 112 consecutive patients who underwent an elective cholecystectomy between January 1997 and December 2000. The procedure was changed in eight ways: the American position, open laparoscopy, reusable trocars, reusable instruments, bipolar coagulation of the cystic artery, intracorporeal ligature of the cystic duct, no use of suction lavage apparatus, and use of a surgical glove as a bag to extract the gallbladder. Complete compliance with the procedure, whether any abnormal operative events or complications occurred, the duration of hospitalization, and the material and labour costs of the procedure were recorded. RESULTS: There were no abnormal operative events. Only two patients suffered from postoperative complications. The mean duration of hospitalization was 55.8 h. Fifteen patients (13.4 per cent) were not hospitalized overnight. The operating costs fell from 560 euros before the study to 330 euros in 2000. CONCLUSION: By applying simple measures, it is possible to decrease the operating room cost of laparoscopic cholecystectomy whilst maintaining good results. Such measures should be applied to other laparoscopic procedures.

Adult↗
PubMed2002

Efficacy of amoxicillin-sulbactam, given twice-a-day, for the treatment of community-acquired pneumonia: a clinical trial based on a pharmacodynamic model.

The present multicenter study reports the results of a clinical trial, designed on the basis of a pharmacodynamic study published previously (Bantar et al., J. Chemother 2000; 12: 223-227) to assess the efficacy of amoxicillin/sulbactam (875 mg/125 mg), given orally twice-a-day for 7 days in the treatment of patients with community-acquired pneumonia (CAP). Eighty-four evaluable subjects older than 19 years with clinical symptoms and features suggestive of CAP, consulting from June 2000 to March 2002 and meeting the PORT risk class I through III, were enrolled in the study. Mean age (y +/- standard deviation) was 46.7 +/- 16.3 and 62% of the patients had some co-morbidity predisposing for CAP. Several individuals (77.4%) fell into a low-risk class (i.e. PORT I or II) and 22.6% of patients belonged to a moderate-risk class at the start of treatment. Six patients (6.45%) had pneumococcal bacteremia. Streptococcus pneumoniae was the organism most frequently isolated (61.9% of all the patients in whom an etiologic diagnosis was made), followed by Haemophilus influenzae. Clinical success was observed in 97.6% of the patients (confidence interval 95%, 94.3%-100%). Almost all the individuals with clinical success became afebrile within the first 3 days of therapy. Ten patients (11.8%) reported mild or moderate adverse events (especially diarrhea) possibly related to the antimicrobial therapy, but this did not lead to withdrawal from the trial. The results of this study suggest that amoxicillin/sulbactam (875 mg/125 mg) is an efficacious and well tolerated option for treating patients with CAP belonging to a low-moderate risk class and support the use of a short, oral (7-day) b.i.d. regimen.

Administration, Oral↗
PubMed2002

[Peri-hepatitis abscess secondary to pelvic peritonitis].

OBJECTIVE: To report the case of a 42-year-old patient referred for exploration of a tumor of the right flank and evidence of inflammation. MATERIAL: and methods. Ultrasonography and computed tomography showed a liver mass associated with a heterogeneous adnexal mass. Serum CA-125 was elevated and ovarian cancer with liver metastasis was suspected. An alternative diagnosis was salpingitis complicated by Fitz-Hugh-Curtis syndrome in this patient wearing an intra-uterine contraceptive device. RESULTS: Exploratory laparoscopy was performed and confirmed the diagnosis of salpingitis complicated by an ovarian abscess and Fitz-Hugh-Curtis syndrome with rare abscess formation. Outcome was favorable after adapted antibiotic treatment. CONCLUSION: Fitz-Hugh-Curtis syndrome can take on an atypical aspect and should be entertained as a possible diagnosis in young women presenting pain of the right flank and fever.

Acute Disease↗
PubMed2001

Transplantation of hepatocytes in nonhuman primates: a preclinical model for the treatment of hepatic metabolic diseases.

BACKGROUND: The transplantation of isolated hepatocytes in large animals, including nonhuman primates, must be evaluated before clinical trials are performed. However, in the absence of large transgenic animals and large-animal (as opposed to small-animal) models of genetic deficiencies, it is difficult to evaluate the fate of transplanted hepatocytes, their localization, survival, and function within the parenchyma of the host liver. In this work, we aimed to develop a technique for delivering hepatocytes to the liver of a nonhuman primate and to evaluate their localization and functionality in the short term. METHODS: A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis) and hepatocytes were isolated. Hepatocytes were labeled in vitro with a recombinant retrovirus expressing the beta-galactosidase gene and returned to the liver by infusion through a portal catheter left in place. Liver biopsies were performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent surgery to define the necessary technical adjustments and to optimize conditions. Six monkeys died. The whole protocol, including the transplantation of genetically marked hepatocytes and procurement of liver biopsies, was performed in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes expressing the beta-galactosidase gene were widely distributed in the portal tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate model for the evaluation of hepatocyte transplantation. We demonstrated the engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7 d after transplantation.

Animals↗
PubMed2001

Pitx2 expression defines a left cardiac lineage of cells: evidence for atrial and ventricular molecular isomerism in the iv/iv mice.

The homeobox gene Pitx2 has been characterized as a mediator of left-right signaling in heart, gut, and lung morphogenesis. However, the relationship between the developmental role of Pitx2 and its expression pattern at the organ level has not been explored. In this study we focus on the role of Pitx2 in heart morphogenesis. Chicken Pitx2 transcripts are present in the left portion of the cardiac crescent and in the left side of the heart tube. Through looping Pitx2 is present in the left atrium, in the ventral portion of the ventricles and in the left-ventral part of the outflow tract. Mouse Pitx2 shows a similar developmental profile of expression. To test whether Pitx2 represents a lineage marker we have tagged the left portion of the chicken cardiac tube with fluorescent DiD. Labeled cells were found at HH16 in the left atrium and in the ventral region of the ventricles and the outflow tract. In the iv/iv mouse model of cardiac heterotaxia Pitx2 was abnormally expressed in the atrial and in the ventricular chambers. Furthermore, altered Pitx2 expression correlated with the occurrence of DORV. Our data reveal the existence of molecular isomerism not only in the atrial, but also in the ventricular compartment of the heart.

Animals↗
PubMed2001

Molecular characterization of the ventricular conduction system in the developing mouse heart: topographical correlation in normal and congenitally malformed hearts.

OBJECTIVES: Within the adult heart, it is convention to distinguish the conduction system and working (atrial and ventricular) myocardium. The adult conduction system (CS) comprises the sinoatrial (SAN), and atrioventricular (AVN) nodes, the atrioventricular bundle (AVB), the bundle branches and the peripheral Purkinje fibers, each of which display distinct functional properties and distinct profile of gene expression. Characterization of the mouse cardiac conduction system during development is rudimentary at present, even though genetically-modified mice are an increasing source of information regarding cardiac function and embryonic heart development. METHODS: We have performed a detailed study of the pattern of expression of myosin heavy chain (MHC), myosin light chain (MLC), troponin I (TnI) isoforms, connexin 43 (Cx43), desmin and alpha-smooth muscle actin (alpha-SMA), in the ventricular conduction system of normal and congenitally malformed mouse hearts (iv background) from embryonic day 14.5 to 19.5. RESULTS: The AVN is characterized by co-expression of MHC and MLC isoforms and no detectable expression of Cx43, desmin or alpha-SMA. The AVB expresses betaMHC and MLC2v, but no alphaMHC, MLC2a, Cx43, desmin or alpha-SMA. The right and left bundle branches display enhanced expression of desmin and alpha-SMA but no Cx43. The normal expression profile is maintained in congenitally malformed hearts such as double-outlet right ventricle and common atrioventricular canal. Three-dimensional reconstruction of the conduction system shows normal arrangement of the bundle branches in congenitally malformed hearts, but abnormal location and/or extension of the AVN. CONCLUSIONS: Molecular characterization allows to follow the development of the CS in both, normal and malformed mouse hearts. Normal phenotypic expression of the CS is independent of heart situs but shows minor modifications in the presence of heart malformations. It is concluded that the AVN derives from the atrioventricular canal myocardium, the bundle of His from the ventricular myocardium, and the bundle branches from the ventricular trabeculations. Our results do not provide evidence to support an extra-cardiac origin of the ventricular CS.

Actins↗
PubMed2001

Engraftment of autologous retrovirally transduced hepatocytes after intraportal transplantation into nonhuman primates: implication for ex vivo gene therapy.

The main impediment to effective ex vivo liver gene therapy of metabolic diseases is the lack of experimental work on large animals to resolve such important issues as effective gene delivery, cell-processing techniques, and the development of appropriate vectors. We have used a nonhuman primate, as a preclinical model, to analyze the limiting steps of this approach using recombinant retroviruses. Seven monkeys (Macaca fascicularis) underwent the complete protocol: their left liver lobe was resected, a catheter was placed in the inferior mesenteric vein and connected to an infusion chamber, and the hepatocytes were isolated, cultured, and transduced with a retroviral vector containing the beta-galactosidase gene. The hepatocytes were harvested and returned to the host via the infusion chamber. Biopsies were taken 4-40 days later. No animal was killed in the course of the experiments. They all tolerated the procedure well. We have developed and defined conditions that permit the proliferation and transduction of up to 90% of the plated hepatocytes. A significant proportion of genetically modified cells, representing up to 3% of the liver mass, were safely delivered to the liver via the chamber. Polymerase chain reaction analysis detected integrated viral DNA sequences and quantitative analysis of the in situ beta-Gal-expressing hepatocytes indicated that a significant amount of transduced hepatocytes, up to 2%, had become integrated into the liver and were functional. These results represent substantial advances in the development of the ex vivo approach and suggest that this approach is of clinical relevance for liver-directed gene therapy.

Animals↗
PubMed2001

MLC3F transgene expression in iv mutant mice reveals the importance of left-right signalling pathways for the acquisition of left and right atrial but not ventricular compartment identity.

Abstract Transcriptional differences between left and right cardiac chambers are revealed by an nlacZ reporter transgene controlled by regulatory sequences of the MLC3F gene, which is expressed in the left ventricle (LV), atrioventricular canal (AVC), and right atrium (RA). To examine the role of left-right signalling in the acquisition of left and right chamber identity, we have investigated MLC3F transgene expression in iv mutant mice. iv/iv mice exhibit randomised direction of heart looping and an elevated frequency of associated laterality defects, including atrial isomerism. At fetal stages, 3F-nlacZ-2E transgene expression remains confined to the morphological LV, AVC, and RA in L-loop hearts, although these appear on the opposite side of the body. In cases of morphologically distinguishable right atrial appendage isomerism, both atrial appendages show strong transgene expression. Conversely, specimens with morphological left atrial appendage isomerism show only weak expression in both atrial appendages. The earliest left-right atrial differences in the expression of the 3F-nlacZ-2E transgene are observed at E8.5. DiI labelling experiments confirmed that transcriptional regionalisation of the 3F-nlacZ-2E transgene at this stage reflects future atrial chamber identity. In some iv/iv embryos at E8.5, the asymmetry of 3F-nlacZ-2E expression was lost, suggesting atrial isomerism at the transcriptional level prior to chamber formation. These data suggest that molecular specification of left and right atrial but not ventricular chambers is dependent on left-right axial cues.

Animals↗
PubMed2001

Divergent expression of delayed rectifier K(+) channel subunits during mouse heart development.

The repolarization phase of the cardiac action potential is dependent on transmembrane K(+) currents. The slow (I(Ks)) and fast (I(Kr)) components of the delayed-rectifier cardiac K(+) current are generated by pore-forming alpha subunits KCNQ1 and KCNH2, respectively, in association with regulatory beta-subunit KCNE1, KCNE2 and perphaps KCNE3. In the present study we have investigated the distribution of transcripts encoding these five potassium channel-forming subunits during mouse heart development as well as the protein distribution of KCNQ1 and KCNH2. KCNQ1 and KCNH2 mRNAs (and protein) are first expressed at embryonic day (E) 9.5, showing comparable levels of expression within the atrial and ventricular myocardium during the embryonic and fetal stages. In contrast, the beta-subunits display a more dynamic pattern of expression during development. KCNE1 expression is first observed at E9.5 throughout the entire myocardium and progressively is confined to the ventricular myocardium. With further development (E16.5), KCNE1 expression is mainly confined to the compact ventricular myocardium. KCNE2 is first expressed at E9.5 and it is restricted already to the atrial myocardium. KCNE3 is first expressed at E8.5 throughout the myocardium and with further development, it becomes restricted to the atrial myocardium. The fact that alpha subunits are homogeneously distributed within the myocardium, whereas the beta subunits display a regionalized expression profile during cardiac development, suggest that differences in the slow and fast component of the delayed-rectifier cardiac K(+) currents between the atrial and the ventricular cardiomyocytes are mainly determined by differential beta-subunit distribution.

Animals↗
PubMed2001

Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis.

BACKGROUND & AIMS: To evaluate how characterization of genetic alterations can help in the elucidation of liver carcinogenesis pathways, 137 tumors were analyzed. METHODS: High-density allelotype, p53, Axin1, and beta-catenin gene mutations were determined. Alterations were analyzed according to clinical parameters. RESULTS: Tumors could be divided into 2 groups according to chromosome stability status. In the first group, demonstrating a chromosome stability, beta-catenin mutation associated with chromosome 8p losses were frequently found as the single genetic alterations. beta-catenin mutations were associated with large tumor size and with negative hepatitis B virus status. In the second group, demonstrating a chromosome instability, the most frequent allelic losses were on chromosome 1p, 4q, 6q, 9p, 13q, 16p, 16q, and 17p; Axin1 and p53 were frequently mutated. All of these alterations, except losses on 6q and 9p, were associated with hepatitis B virus infection. P53 mutations, 17p, 13q losses, and a high value of the fractional allelic loss index were associated with poor differentiated tumors, independently of risk factors. Finally, in the whole series, chromosome 9p and 6q losses were associated with poor prognosis. CONCLUSIONS: Two main pathways defined by genetic alterations show different risk factors and clinical characteristics. Furthermore, loss of chromosome 9p or 6q is an independent prognostic indicator.

Adolescent↗
PubMed2001

Differential expression of KvLQT1 and its regulator IsK in mouse epithelia.

KCNQ1 is the human gene responsible in most cases for the long QT syndrome, a genetic disorder characterized by anomalies in cardiac repolarization leading to arrhythmias and sudden death. KCNQ1 encodes a pore-forming K+ channel subunit termed KvLQT1 which, in association with its regulatory beta-subunit IsK (also called minK), produces the slow component of the delayed-rectifier cardiac K+ current. We used in situ hybridization to localize KvLQT1 and IsK mRNAs in various tissues from adult mice. We showed that KvLQT1 mRNA expression is widely distributed in epithelial tissues, in the absence (small intestine, lung, liver, thymus) or presence (kidney, stomach, exocrine pancreas) of its regulator IsK. In the kidney and the stomach, however, the expression patterns of KvLQT1 and IsK do not coincide. In many tissues, in situ data obtained with the IsK probe coincide with beta-galactosidase expression in IsK-deficient mice in which the bacterial lacZ gene has been substituted for the IsK coding region. Because expression of KvLQT1 in the presence or absence of its regulator generates a K+ current with different biophysical characteristics, the role of KvLQT1 in epithelial cells may vary depending on the expression of its regulator IsK. The high level of KvLQT1 expression in epithelial tissues is consistent with its potential role in K+ secretion and recycling, in maintaining the resting potential, and in regulating Cl- secretion and/or Na+ absorption.

Animals↗